The present invention provides for the use of hyaluronic acid and the derivatives thereof in forming coatings for electronic and microelectronic instruments and their parts, to inhibit adhesion of microorganisms (e.g., bacteria) to their surfaces.
In many areas of technology, it is known that the adhesion to a surface of an instrument of microorganisms and consequent growth of the microorganisms, such as bacteria, can impair the efficacy of such instruments.
Bacterial colonization may lead to the formation of a biofilm and to the consequent deposit of mineral substances (Costerton, J. W. et al., xe2x80x9cMicrobial Biofilmsxe2x80x9d, Ann. Rev. Microbiol., 49:711-745, 1995; Costerton J. W., xe2x80x9cOverview of Microbial Biofilmsxe2x80x9d J. Indust. Microbiol. 15, 137-140, 1995).
The bacteria forming the biofilm are bound together in a sticky web of polysaccharide fibers which connect cells into strands and anchor them to a substrate and to each other. Within this microcosm, anaerobic and aerobic bacteria thrive side by side and interact to render their structure even stronger. Some release hydrogen, others reduce carbon dioxide into methane, others feed on dead cells.
The bacteria in the biofilms are, therefore, morphologically and metabolically different from the free-floating variety and the polysaccharide coating they produce seems to act as a coat of armor making it more difficult for them to be attacked by antimicrobial agents than those which are not organized into a similar structure.
Moreover, it seems that any bacterium that manages to find a surface to stick to is able to form a biofilm, activating specific genes for the production of polysaccharides and other substances necessary for the organization of a colony.
Besides leaving a deposit of mineral substances, the biofilm can cause surfaces to become corroded, for instance by altering the pH or by means of oxide reduction reactions. Indeed, anaerobic bacteria organized into biofilms are able to reduce sulfur into hydrogen sulfide, a corrosive agent that can perforate conduits, while aerobic bacteria corrode metals by oxidation. This is a problem in the field of electronics, and even more so in that of microelectronics where the increasingly tiny circuits that are being made use of are ever so more susceptible to the presence of contaminants, including microorganisms. Indeed, their presence can create short circuits between adjacent electric parts (Perera A. H.; Satterfield M. J. xe2x80x94Micromasking of plasma-etching due to bacteria. A yield detractor for ULSI; IEEE Transactions on semiconductor manufacturing, 1996, V9, N4 (November), P 577-580) besides corroding the surfaces.
The main problem with biofilm formation on microchips is that it acts as a conductor, thus interfering with electric signals. Electronic instruments are often wrapped, coated or closed within containers to protect them from damp, heat and corrosive agents. There are therefore various known coatings for electronic equipment, such as heat-resistant polyester, polycarbonate, nylon, polystyrene and PVC films, insulating fluorosilicone polymer for semiconductors (WO 96/34034); protective coatings made of fluorinated quinoline or ceramic (WO 92/03488).
However, such coatings only represent a mechanical barrier and are insufficient to protect the instrument from bacterial attack.
One of the natural compounds known to date to have properties which inhibit bacterial adhesion in the biomedical and health care field is hyaluronic acid, a natural polysaccharide constituted by a linear sequence of D-glucuronic acid and N-acetyl-D-glucosamine. It is present in the connective tissue, in the synovial fluid of joints, in the skin, in the umbilical cord and in the vitreous humor of the eye.
However, no one has ever thought of using to advantage hyaluronic acid or the derivatives thereof in sectors other than the biomedical one, for example in electronics or in microelectronics to coat instruments which might otherwise be prone to malfunction because of the bacterial colonies described above.
The present invention is concerned with preventing the formation of biofilms on the various surfaces and parts of electronic and microelectronic instruments, and the parts thereof, by inhibiting the adhesion of microorganisms such as bacteria to the various surfaces and parts of the electronic instruments, by coating at least a portion of a surface of such instruments or parts thereof with a coating composition containing hyaluronic acid or a derivative thereof, having the ability to inhibit bacterial adhesion.
Thus, in a first aspect, the present invention relates to an electronic or microelectronic instrument having on at least a portion of a surface thereof a coating that contains hyaluronic acid or a derivative thereof having an ability to inhibit the adhesion of microorganisms.
In a further aspect, the present invention relates to a method of providing an antimicrobial coating on at least a portion of a surface of an electronic or microelectronic instrument, or a part thereof, which method comprises:
applying to the portion of the surface of the electronic or microelectronic instrument or the part thereof, a coating that contains hyaluronic acid or a derivative thereof having the ability to inhibit the adhesion of microorganisms.
Also, the present invention relates to the use of hyaluronic acid or a derivative thereof, having the ability to inhibit the adhesion of microorganisms, to coat at least a portion of a surface of an electronic or microelectronic instrument or a part thereof.
The hyaluronic acid derivative employed according to the invention can be, e.g. and preferably, selected from the group consisting of total and partial esters of hyaluronic acid, esters of polyvalent alcohols of hyaluronic acid, inner esters of hyaluronic acid, sulfated esters of hyaluronic acid, and succinyl derivatives of hyaluronic acid.
Preferably, said portion of the surface thereof that is coated with said coating containing hyaluronic acid or the derivative thereof is resistant to adhesion by microorganisms.
By applying said hyaluronic acid or the derivatives thereof according to the invention corrosion on the portion of the surface of the electronic or microelectronic instrument or a part thereof that is coated with said hyaluronic acid or derivative thereof is preferably prevented.
It is also preferred that said coating is applied by using a plasma coating technique.
An advantage of the present invention on an industrial level, is the extreme thinness of the protective coatings provided herein compared to known coatings. For example, there is provided herein a method of applying the same coatings under contaminant-free conditions which gives even coverage of the surfaces regardless of the geometry of the surface or part of the electronic or microelectronic instrument being coated. Accordingly, a method of providing such instruments with a protective coating is also contemplated herein, as is the use of the resulting coated electronic and microelectronic instruments.
Exemplary of the coated electronic and microelectronic instruments and parts thereof, that can be provided according to the present invention, wherein a part of a surface thereof or a part thereof is coated according to the invention with a coating comprising hyaluronic acid, or a derivative thereof having the ability to inhibit the adhesion of microorganisms, are integrated microcircuits, semiconductors, connectors and terminators, memory and storage, acceleration and expansion boards, docks for boards and microchips, spacer bars for circuits, and electronic instruments intended to be inserted into the human body or in its external cavities, such as audiological aids (e.g., hearing aids), vocal aids, pace-makers and probes.
The present invention provides for the use of hyaluronic acid and the derivatives thereof in coatings to inhibit the adhesion of microorganisms to the surfaces of electronic and microelectronic instruments and their parts.
The hyaluronic acid used in the present invention may be obtained by extraction, fermentation or synthesis and preferably contains the fractions described in patent Nos. EP 0138572, EP 0535200, and WO 97/22629. The preferred hyaluronic acid derivatives are those described in patent Nos. U.S. Pat. No. 4,851,521 (e.g., hyaluronic acid esters), EP 0265116 B1 (e.g., esters of polyvalent alcohols), EP 0341745 B1 (e.g., crosslinked esters of hyaluronic acid), WO 95/25751 (e.g., sulfated derivatives of hyaluronic acid), and WO 96/35720 (e.g., succinyl derivatives of hyaluronic acid).
A suitable process by which the surfaces of such instruments and parts can be coated is described in international patent application No. WO 96/24392.
In patent application No. WO 96/24392 a xe2x80x9cplasma coatingxe2x80x9d process is provided for the coating of objects used in the fields of health care, surgery and diagnostics with a thin layer of polymers including hyaluronic acid and the derivatives thereof, firmly bound to the substrate to enhance biocompatibility and the smoothness of the coated surfaces and to inhibit adhesion by the cells or bacteria present in the biological fluids.
The ability of hyaluronic acid and its derivatives to inhibit adhesion by cells is demonstrated in the examples given in international patent No. WO 96/24392, which describes microscopic observation of the surfaces of coated biomedical objects which have been kept in contact with cell suspensions in given conditions for suitable lengths of time.
The following examples are provided to aid those desiring to practice the instant invention, with examples 1-3 describing certain coating techniques used on some microelectronic instruments, and example 4 providing an example of the problem of microbial adhesion to microelectronic parts. These provided examples are not, however, to be construed to be limiting to the instant invention, as those skilled in the art realize that there are various changes can be made in the embodiments of the following examples without departing from the spirit or scope of the instant discovery.